The newly constructed "six gene" avian-human influenza A reassortant viruses derived by mating the avian influenza A/Pintail/79 or A/Mallard/76 virus with the human influenza A/Korea/82 wild type virus were shown to be satisfactorily attenuated and immunogenic in monkeys prior to evaluation of these reassortants in man. The RNA 1 and NS genes, but not the M gene, of the A/Pintail/79 virus contribute to the host range restriction of this virus in monkeys. In this regard the genetic basis for host range restriction of the avian influenza A/Pintail/79 virus reassortants differs from that of the previously studied avian influenza A/Mallard/78 virus reassortants in which the avian influenza M gene plays a major role in attenuation. Because different genes in different avian influenza A viruses appear to be responsible for host range restriction it may be possible to construct a "composite" avian influenza donor virus with 4 or more attenuating "internal" genes (derived from different avian influenza A viruses) in order to ensure genetic stability of reassortant vaccine viruses. The "six gene" influenza A ca reassortant virus derived from the influenza A/Ann Arbor/6/60 ca donor virus and the human influenza A/Korea/82 wild type virus, which replicates efficiently in vitro at 37 degrees C, was greatly restricted in replication in the lower respiratory tract (37 degrees C) of the chimpanzee. This indicates that the A/Ann Arbor/6/60 ca donor virus has sustained host range mutations during passage in chick kidney cells. Similarly, two different avian-human influenza A reassortant viruses were greatly restricted in the lower respiratory tract of the chimpanzee, confirming the restriction of replication of these reassortants in a non-human primate closely related to man.